Clinical variability of Stickler syndrome with a COL2A1 haploinsufficiency mutation: implications for genetic counselling

University of Zurich, Zürich, Zurich, Switzerland
Journal of Medical Genetics (Impact Factor: 5.64). 05/2000; 37(4):318-20. DOI: 10.1136/jmg.37.4.318
Source: PubMed
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Available from: Beat Steinmann, Dec 19, 2013
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    ABSTRACT: Collagen is the most abundant protein in the human body. Collagen forms a major part of connective tissue, which can be described as the supportive tissue of the organs of the body. Defect in collagen causes various syndromes, including stickler syndrome. Here, stickler syndrome associated 11 human collagen proteins retrieved from National Center for Biotechnology Information (NCBI) Entrez protein database are characterized by using proteomics tools and online proteomics servers to give a detailed description of stickler syndrome-causing human collagen proteins. Primary structure analysis shows that all the 11 stickler syndrome-causing collagen proteins are rich in glycine (23-28%) and proline (16-18%) residues. The computed pI value indicates that the collagen proteins, NP_542197.1, NP_542196.1, NP_001845.2, NP_542411.1, AAF04726.1, AAF04725.1 and AAF04724.1, are acidic, (pI 7), and the protein, NP_001835.2 is neutral (pI =~ 7) in character. The very low Aliphatic Index (AI) (38-50) infers that the collagen proteins may become unstable at high temperature. Based on the Instability Index, the Expasy’s ProtParam classifies the collagen proteins as stable. Secondary structure analysis shows that all the 11 collagen proteins are found to be of predominant coil structure content (100%), and the Secondary Structure Content Prediction server (SSCP) classifies as irregular secondary structure class. The irregular structure of collagen proteins is due to the rich content of more flexible glycine and hydrophobic proline amino acids. SOSUI server predicts one transmembrane region (IRLGAPQSLVLLTLLVAAVLRCQ) in alpha 1 type II collagen proteins. The predicted transmembrane region is visualized and analyzed using helical wheel plot generated by EMBOSS pepwheel tool and it is found that the helical wheel consists of hydrophobic residues. The hydrophobicity of predicted transmembrane region is also well-documented by the Kyte and Doolittle mean hydrophobicity profile.
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